Is new MS research the real thing, or a media-driven frenzy?

Cure vs. Hype: 'I had patients in tears'

Luanne Metz, director of the multiple sclerosis clinic at the faculty of medicine at the University of Calgary, holds a model of the human brain

Photograph by: Todd Korol for Canwest news Service
, National Post

For long-suffering multiple sclerosis patients, it seemed like a miracle: a relatively simple new explanation for what causes the often-crippling disease, and an equally straightforward fix.

Indeed, glowingly positive Canadian media accounts of work by Italy's Dr. Paolo Zamboni, who says the disease can be treated by unblocking veins from the brain, have triggered a sensation across the MS world -- and raised questions about how journalists and scientists portray medical research to the public.

Clinics throughout Canada and the United States have been deluged with calls and emails from patients eager to learn more or demanding immediate treatment with the new technique, often bringing the offices' regular work to a halt, physicians say.

Some doctors report that patients have gone off their medication, with potentially long-term negative implications. Others have talked of taking out loans or even selling their houses to fund the experimental therapy. Almost overnight, the MS Society directed hundreds of thousands of dollars in funding to study of the new concept.

Meanwhile, neurologists trying to explain the limitations of Dr. Zamboni's findings have faced sometimes angry recriminations from patients desperate for a cure.

"Many of the callers were very abusive, right from the start," said Dr. Luanne Metz, director of the Foothills Hospital MS clinic in Calgary. "Nasty to the nurses, accusing us of withholding treatment or playing Big Brother and not letting people have what they want, and arguing and arguing and arguing."

MS specialists blame the over-heated response in large part on that CTV documentary and an accompanying newspaper report, calling the stories one-sided depictions of preliminary, unproven research, including the treatment Dr. Zamboni evocatively terms the "Liberation" procedure.

At best, his work represents a promising new way of looking at MS that requires much more validation and testing before it can be widely applied, experts say. At worst, the more rigorous investigation now getting underway will show it to be a scientific dead end.

Most MS neurologists interviewed recently said they welcome the expanded research into Dr. Zamboni's theory, if only to settle the controversy; others lament what they consider a media-driven distraction. "There have been reverberations across the world as a result of that media story," said Dr. Mark Freedman, a neurologist at Ottawa Hospital and a top MS researcher. "I think there are going to be millions of dollars spent now to follow a hoax.... If I thought for one instant there was substance to this, I'd be all over it. But there really is very, very vague backing for the whole theory."

M e a n w h i l e , D r. Pa u l O'Connor, medical advisor to the MS Society of Canada, has joined an international expert panel the Italian society put together to "audit" Dr. Zamboni's findings. Canada has much at stake in the affair, with up to 75,000 patients and one of the world's highest rates of MS. The disease, triggered by damage to the brain's "myelin" coating, causes symptoms ranging from blurred vision to paralysis. Science to date has suggested that the cause is an autoimmune response, the body's immune system turning on itself.

Drugs are available to attack the inflammation that damages the myelin, decrease the severity and length of relapses and treat specific symptoms of MS, such as spasticity or pain, though their effectiveness is limited and side effects can be nasty. Dr. Zamboni, a vascular surgeon whose work would normally have nothing to do with MS, became interested after his wife was diagnosed with the illness. He says ultrasound scans of her head and those of other patients point to a novel new theory of how the illness occurs. Essentially, the surgeon hypothesizes that veins draining blood from the brain become narrowed in MS patients, slowing the blood flow and causing backups to the brain, which in turn prompt inflammation and the resulting myelin damage.

His team operated on his wife and others in an effort to open up their blockages -- which he dubs chronic cerebrospinal venous insufficiency (CCSVI) -- with an "angioplasty," the insertion of a tiny balloon that is inflated inside the affected vessels. Dr. Zamboni says his wife has been symptom-free for three years, and he claims to have successfully treated many other patients, too.

The report on CTV's W5 program eloquently recounted the surgeon's compelling personal story and voyage of discovery, adding interviews with patients who have undergone the procedure and feel all but cured, as well as clips from supportive doctors who are working with the Italian.

A front-page Globe and Mail piece on the topic ran the same Saturday. Neither quoted any of the many physicians who are skeptical of Dr. Zamboni's research, though Dr. Freedman says the CTV reporter did ask his opinion earlier. By Monday morning, hundreds of MS patients were flooding the phone lines of their local clinics, doctors say.

At Dr. Metz's Calgary office, staff were so busy handling anxious Zamboni calls, patients with other, serious concerns had trouble getting through, she said. Some stopped taking their drugs, now convinced the real problem was vein narrowings. Going off one key medication, Tysabri, could have lifelong consequences, as patients who stop and start it again often develop allergies to the drug, Dr. Metz said. Other patients, used to a long string of hopeful "breakthroughs" that turned out to be flops, reacted more cautiously to the news, but had to cope with friends and family convinced they should take advantage of this apparent new remedy, said the neurologist.

"I had patients in tears because they know this is not a treatment yet, not a cure yet, but they have family members pushing them to go to other countries and get things done."

The Winnipeg MS clinic had to stay open two or three hours later than usual many days recently as every patient insisted on a lengthy discussion of the news. "It was presented as very new and exciting research and ready to go," said neurologist Dr. Ruth Ann Marrie, the clinic's director. "Those stories generated an enormous amount of hope."

Some of Dr. Freedman's patients said they were heading to Italy to try to obtain the surgery from Dr. Zamboni's team, including one patient who had fought hard to be part of a clinical trial the Ottawa clinic was planning, then promptly dropped out. U.S. patients mused about taking out loans or selling their homes to pay the $80,000 cost of undergoing the surgery at a California hospital, said Dr. Jack Burks, a New Jersey neurologist and medical advisor to the Multiple Sclerosis Association of America.

"If it doesn't work, after the research is done, they still have MS, but they've lost their house," he noted in an interview. "That's not very good."

The MS Society of Canada also received a flurry of calls from patients and, by that first Monday, had announced it was now offering an unlimited number of grants of up to $200,000 for studies to try to replicate Dr. Zamboni's findings. Yves Savoie, the organization's CEO, denied rumours that major donors had threatened to pull their money if it was not redirected to CCSVI. He acknowledged, though, the speedy decision was unprecedented in the group's history, a response to the widespread interest in Dr. Zamboni's "compellingly simple" treatment.

"You have a researcher who hypothesizes something and dares call it the Liberation procedure," Mr. Savoie noted. "It was already branded as something that sounded like a cure."

Indeed, the medical community seems under intense pressure to embrace the Italian research. One patient advocate in Edmonton, Ashton Embry, suggested on a recent blog posting that neurologists are resisting the ideas only because "they would essentially be cut out of the action when it comes to treating MS patients."

Teresa Woo, 41, from McLennan, Alta., started an online petition calling for government funding of the procedure, and has already gathered 9,000 signatures, believing Dr. Zamboni has found something close to a cure. She became emotional upon viewing the televised report two months ago.

"I started crying and I continued to cry through the whole thing," Ms. Woo recalls.

"These [Canadian neurologists] think they know it all, and they don't: they really answer to the drug companies," she said in an interview. "They should not have the right to tell us we can't do this. It is my right as a human being to try this."

MS specialists, however, call the media irresponsible for failing to take a more skeptical look at the research and prematurely raising the hopes of patients such as Ms. Woo.

The affair underlines generally the perils of journalists failing to carefully scrutinize the claims of medical science, especially in an era when researchers compete aggressively for funding and bragging rights, said Dr. Ian Mitchell, a bio-ethicist at the University of Calgary.

He notes that Dr. Zamboni is an enthusiastic proponent of his own research, was emotionally involved because of his wife's role and has already given his procedure a vivid nickname. "You'd never be allowed to have a drug called Liberationex, it's such an emotive title. Usually, flags would go up," said Dr. Mitchell, who is also a pediatrician. But "[the research] was portrayed uncritically as a modern miracle."

As it turns out, many questions are being raised about Dr. Zamboni's conclusions, and even he has said there is an urgent necessity for outside study of his ideas, telling the Ottawa Citizen in a letter to the editor that patients "need to have clear answers."

The underpinning of the vascular theory is a study that compared 65 MS patients to 235 non-MS controls. Vein narrowing -- or stenosis -- showed up in ultrasound scans of all the multiple sclerosis subjects, and none of the others, he reported.

Canadian experts agree the findings are intriguing, and Mark Haacke, a leading medical physicist and MRI expert at Hamilton's McMaster University, has said the Zamboni hypothesis is a "logical explanation" for how MS works. Others, however, say interpreting scans of such veins is fraught with difficulty, and say there is no proof the vein stenosis, if it does exist, is a cause of MS, as opposed to just being a common, non-causal facet of the disease.

The most controversial evidence, though, is the paper he published last month on the actual Liberation treatment, as provided to 65 patients. The results were mixed. Dr. Zamboni reports there was significant improvement on a scale measuring certain MS symptoms such as leg function in the "relapsing/ remitting" group of patients -- those with the mildest form of the disease, who normally can go into remission for months or years at a time. The more pronounced secondary and primary progressive patients had limited improvement after six months, but none at 18 months, he reported.

A higher proportion of the relapsing/remitting patients were in remission in the 18 months after the surgery than in the year before, but the annual rate of relapses for the group was unchanged. The veins narrowed again in almost half the patients. Dr. Burks calls the outcomes "encouraging," if tentative.

Neurologists outline a string of limitations to the study, though. There was no "control" group of patients who did not get the surgery and whose outcomes could be compared to the Liberation patients. It was not a "blinded" trial, meaning that the patients, and their doctors, all knew they had received the procedure, opening up the possibility of placebo effect. And all the patients continued to take their disease-modifying drugs, making it difficult to separate out what, if anything, improved their condition.

"We have spent a lot of time and effort and energy on what is essentially media hype," Dr. Pierre Duquette, a University of Montreal neurologist, said of the Italian work. "It is essentially a negative study."

Also unusual is Dr. Zamboni's treatment of his own wife, though the actual procedure appeared to have been carried out on her by another doctor. "You'd lose your licence" as a Canadian physician for treating a close family member under anything but emergency conditions, Dr. Marrie said.

Medical history does record cases of game-changing discoveries from outsiders. Peptic ulcers were considered to be a result of acid accumulation in the gut, for instance, until an Australian scientist discovered in the 1980s that most were actually caused by a bacteria. He later won the Nobel prize.

Health science is also replete, though, with apparent breakthroughs that are proven useless or dangerous under more intense study. Neurologists point to the history of so-called EC/IC bypass surgery. Extremely popular in the early 1980s, it involved taking an artery from under the scalp and grafting it onto the brain to circumvent clogged arteries in patients at risk of stroke.

A Canadian-led trial finally put the surgery to rigorous testing, however, and found that it actually made strokes more likely. Almost overnight, the EC/IC clinics that had cropped up across North America closed their doors.

Dr. Tony Traboulsee at the UBC Hospital MS clinic is planning one of a handful of studies that will examine whether the Zamboni theory falls into the same category -- or is a bonafide breakthrough. His team will first look for evidence of the vein narrowing, then study the treatment. A verdict on the Italian scientist's work is expected in a year or two.

"What Dr. Zamboni did was tantalize us," Dr. Traboulsee said. "It was intriguing, but it was not proof."

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BACK STORY

MS IN BRIEF

What is multiple sclerosis? Lesions damage the brain's myelin insulation, sometimes short-circuiting messages from the brain to other parts of the body.

What are the symptoms? A range from fatigue to blurred vision, dizziness, impaired mobility, slurred speech and paralysis.

THE CURRENT SCIENCE AROUND MS

Cause Most experts believe it is an autoimmune disease, where white blood cells meant to fight disease attack the body itself, causing inflammation that damages the myelin and underlying nerves.

Treatment There are drugs designed to attack the underlying inflammatory triggers of the disease; curb the severity and duration of relapses; and lessen certain symptoms, such as fatigue, spasticity and pain. Their effects are somewhat limited, though, and must be taken by injection or infusion. Research is also under way in Ottawa and elsewhere on using stem cells to rebuild patients' damaged central nervous systems.

News Studies published in the New England Journal of Medicine on Wednesday concluded that the first two oral drugs for MS, Cladribine and fingolimod, are more effective than a placebo and at least one existing drug in reducing the annual rate of attacks and the number of brain lesions visible on MRIs.

DR. PAOLO ZAMBONI'S APPROACH TO MS

Cause Dr. Zambonibelieves the disease is triggered by a narrowing or blockage of the veins that drain blood from the brain, resulting in a back-up of blood and excess iron in the brain, which he suggests causes the inflammation and myelin damage. The phenomenon, termed chronic cerebrospinal venous insufficiency (CCSVI), is unique to MS patients, he says.

Treatment Dr. Zamboniand a California physician have tried different but similar techniques for unblocking the narrowed veins. One involves angioplasty, inflating a tiny balloon inside the affected blood vessels, the other installing a stent -- a permanent device -- that holds the vein open. Dr. Zamboni published a study suggesting the angioplasty treatment -- which he dubbed the Liberation procedure -- improved symptoms for some patients and reduced the percentage who had relapses. Critics note there was no control group with which to compare the therapy and no "blinding" to prevent the risk of a placebo effect.

News Dr. Zamboni and other doctors involved in researching his theories are to appear at a forum on CCSVI at McMaster University on Feb. 7. Organizers say they hope it will become an annual event.

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